As I walk back to my car after a long and exciting day in class and lab, I have to pay attention to my environment for multiple reasons. First, I am clumsy and very likely to trip if I don’t. Second, I have to not only remember where my car is, but also know where I am in relation to it. As I scan the buildings around me, I am able to update my awareness of where I am based on everything I sense around me. Using sensory and spatial information (where am I?) together with memory (where is my car?) to drive behavior (walking in the correct direction to my car) is just one example demonstrating the incredible computing power of the brain.

Figure 1: Finding my car, the eternal struggle

Figure 1: Finding my car, the eternal struggle

How is my brain getting me to my car? To answer this question, Dr. György Buzsáki, Biggs Professor of Neural Sciences at NYU and this week’s Dart NeuroScience Seminar Series speaker, will tell us about theta oscillations in the hippocampus, the brain’s center for memory and spatial navigation. As shown by extensive research from Dr. Buzsáki’s lab and other labs, hippocampal theta oscillations, the 4-11 Hz collective activity of large neuronal populations, are essential for memory retrieval and spatial navigation, and deficits in neural oscillations in general have been associated with many cognitive deficits (for more information, Dr. Buzsáki’s review of theta oscillations can be found here).

Dr. Buzsáki and others hypothesize that the generation of theta oscillations brings the activity of sensory-activated and memory-activated neurons together, organizing individual spiking neurons into larger, oscillating networks that can accomplish a variety of computational tasks, including by communicating with other networks in distant brain regions. As elegantly described in the research goals on Dr. Buzsáki’s lab website, just as we put together words to form sentences, single-cell activity patterns are organized into overarching neural oscillations. Then, just as entire sentences express more complex meanings than do single words, neural oscillations convey more and accomplish more than the activity of only a few neurons.

Thus, by studying neural oscillations and how they are generated and maintained, Dr. Buzsáki studies neural syntax, the language of the brain, and he and his lab have greatly advanced our understanding of the nature and importance of hippocampal theta oscillations. In recent work from his lab, Dr. Eran Stark and colleagues recorded extracellularly from excitatory pyramidal cells (PYR) and inhibitory, parvalbumin-expressing interneurons (PV) in the hippocampus and neocortex of awake, freely-moving mice. At the same time, using optogenetic methods, channelrhodopsin-expressing PYR or PV were stimulated with a time-varying chirp pattern, a sinusoidal pattern of linearly increasing frequency.

These experiments highlighted two key observations. First, while direct PYR stimulation led to PYR spiking in a wide range of stimulation frequencies, PV stimulation (and therefore indirect PYR inhibition) led to suppression of PYR activity except during theta-frequency PV stimulation. Then, PV stimulation actually led to PYR theta-frequency spiking, indicating resonance selectively of theta-frequency activity patterns.

Figure 2: PV activation leads to theta-frequency PYR activity during theta-frequency stimulation

Figure 2: PV activation led to theta-frequency PYR activity during theta-frequency stimulation

Second, during PV stimulation, PYR spiking occurred specifically at the trough of the chirp-pattern input. This trough corresponded to when stimulation of PV was low and inhibition of PYR was removed. Thus, theta-frequency PV stimulation led to rebound spiking of PYR. Both theta resonance and PYR rebound spiking were shown to be dependent on PYR HCN channels, which typically activate at hyperpolarizing currents and allow positive current flow.

Figure 3: Application of ZD7288, an HCN inhibitor, blocks PYR theta-frequency activity during PV stimulation

Figure 3: Application of ZD7288, an HCN1-channel inhibitor, blocked PYR theta-frequency activity during PV stimulation

Overall, this research by Drs. Stark and Buzsáki demonstrates that in hippocampal and cortical populations, there is a strong ability and preference for passing theta-frequency activity from PV to PYR. With how important theta oscillations are for a variety of functions, both cells and networks are endowed with properties that facilitate the communication of theta activity, and as Drs. Stark and Buzsáki hypothesize, theta-frequency PYR rebound spiking could play a critical role in recruiting downstream networks in a time- and PV-activity-dependent manner. Because of this work, we are learning more and more about the syntactic rules that dictate how our brains make meaning, and it will be incredibly exciting to see what new findings about neural oscillations will emerge in the coming months and years.

If thinking about neural oscillations and syntax resonates with you, please come to “Brain oscillations organize neural syntax,” a seminar with Dr. Buzsáki at 4pm on Tuesday, January 13th, in the Farquhar Conference Room of the Center for Neural Circuits and Behavior. We hope to see you there!


Tammy Tran is a first-year UCSD Neurosciences graduate student currently rotating in Dr. Maryann Martone’s lab. She is shamelessly passionate about the minions from Despicable Me and currently has three toy ones on her desk. When she’s not thinking about neuroscience, she thinks about art and likes going to museums.


Figure 1: Courtesy of http://nexus5.wonderhowto.com/how-to/find-your-missing-parked-car-using-your-nexus-without-doing-any-work-0151269/

Review: Buzsaki, G. Theta Oscillations in the Hippocampus. Neuron. 2002 Jan 31; 33(3):325-340. doi: 10.1016/S0896-6273(02)00586-X

Lab Website: http://www.buzsakilab.com/

Article: Stark E, Eichler R, Roux L, Fujisawa S, Rotstein HG, Buzsáki G. Inhibition-induced theta resonance in cortical circuits.  Neuron. 2013 Dec 4; 80(5):1263-76. doi: 10.1016/j.neuron.2013.09.033.

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